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dc.contributor.authorBacchus-Souffan, C
dc.contributor.authorFitch, M
dc.contributor.authorSymons, J
dc.contributor.authorAbdel-Mohsen, M
dc.contributor.authorReeves, DB
dc.contributor.authorHoh, R
dc.contributor.authorStone, M
dc.contributor.authorHiatt, J
dc.contributor.authorKim, P
dc.contributor.authorChopra, A
dc.contributor.authorAhn, H
dc.contributor.authorYork, VA
dc.contributor.authorCameron, DL
dc.contributor.authorHecht, FM
dc.contributor.authorMartin, JN
dc.contributor.authorYukl, SA
dc.contributor.authorMallal, S
dc.contributor.authorCameron, PU
dc.contributor.authorDeeks, SG
dc.contributor.authorSchiffer, JT
dc.contributor.authorLewin, SR
dc.contributor.authorHellerstein, MK
dc.contributor.authorMcCune, JM
dc.contributor.authorHunt, PW
dc.date.accessioned2021-05-03T23:54:25Z
dc.date.available2021-05-03T23:54:25Z
dc.date.issued2021-01-01
dc.identifierpii: PPATHOGENS-D-20-01673
dc.identifier.citationBacchus-Souffan, C., Fitch, M., Symons, J., Abdel-Mohsen, M., Reeves, D. B., Hoh, R., Stone, M., Hiatt, J., Kim, P., Chopra, A., Ahn, H., York, V. A., Cameron, D. L., Hecht, F. M., Martin, J. N., Yukl, S. A., Mallal, S., Cameron, P. U., Deeks, S. G. ,... Hunt, P. W. (2021). Relationship between CD4 T cell turnover, cellular differentiation and HIV persistence during ART. PLOS PATHOGENS, 17 (1), https://doi.org/10.1371/journal.ppat.1009214.
dc.identifier.issn1553-7366
dc.identifier.urihttp://hdl.handle.net/11343/272753
dc.description.abstractThe precise role of CD4 T cell turnover in maintaining HIV persistence during antiretroviral therapy (ART) has not yet been well characterized. In resting CD4 T cell subpopulations from 24 HIV-infected ART-suppressed and 6 HIV-uninfected individuals, we directly measured cellular turnover by heavy water labeling, HIV reservoir size by integrated HIV-DNA (intDNA) and cell-associated HIV-RNA (caRNA), and HIV reservoir clonality by proviral integration site sequencing. Compared to HIV-negatives, ART-suppressed individuals had similar fractional replacement rates in all subpopulations, but lower absolute proliferation rates of all subpopulations other than effector memory (TEM) cells, and lower plasma IL-7 levels (p = 0.0004). Median CD4 T cell half-lives decreased with cell differentiation from naïve to TEM cells (3 years to 3 months, p<0.001). TEM had the fastest replacement rates, were most highly enriched for intDNA and caRNA, and contained the most clonal proviral expansion. Clonal proviruses detected in less mature subpopulations were more expanded in TEM, suggesting that they were maintained through cell differentiation. Earlier ART initiation was associated with lower levels of intDNA, caRNA and fractional replacement rates. In conclusion, circulating integrated HIV proviruses appear to be maintained both by slow turnover of immature CD4 subpopulations, and by clonal expansion as well as cell differentiation into effector cells with faster replacement rates.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleRelationship between CD4 T cell turnover, cellular differentiation and HIV persistence during ART
dc.typeJournal Article
dc.identifier.doi10.1371/journal.ppat.1009214
melbourne.affiliation.departmentDoherty Institute
melbourne.affiliation.departmentInfectious Diseases
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titlePLoS Pathogens
melbourne.source.volume17
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1490524
melbourne.contributor.authorLewin, Sharon
melbourne.contributor.authorCameron, Paul
melbourne.contributor.authorSymons, Jori
dc.identifier.eissn1553-7374
melbourne.identifier.fundernameidNATIONAL INSTITUTE OF HEALTH, 1RO1AI116368-01A1 / 8732sc
melbourne.accessrightsOpen Access


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